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Integrating theories of the etiology of Crohn's Disease On the etiology ofCrohn's Disease: Questioning the Hypotheses.

William M. Chamberlin, Saleh A. Naser

Med Sci Monit 2006; 12(2): RA27-33

ID: 445257

The most prominent theory describes the Crohn's Syndrome as a dysregulated,inappropriate immune response to otherwise innocuous bowel flora in a genetically susceptible host. Theautoimmune theory assumes that a specific infectious agent does not exist. Data from mouse models, impairmentof the mucosal epithelial barrier and the influence of gut flora are used to support the autoimmune theory.Critics claim that the dysregulated immune responses are not the primary disorder but secondary to anunderlying infection. Two other theories are also consistent with the same data. The immunodeficiencytheory hypothesizes that defects in innate immunity leading to compensatory immune processes underliethe Crohn's phenotype and suggests that therapy should stimulate immunity rather than suppress it. Themycobacterial theory proposes that Mycobacterium avium subspecies paratuberculosis is one of the causesof the Crohn's Disease syndrome. Mycobacterial molecules dysregulate immune signaling pathways as partof the organisms'evolved survival strategy. If MAP were to initiate the dysregulated immune responsethen the necessity to hypothesize that commensal gut flora provide the antigenic stimulus would be moot.Commensal bacteria would be relegated to a secondary role of modifying the immune response rather thanoccupying the central role of providing the initiating antigens. Critics claim that MAP is merely a secondaryinvader. The three theories differ primarily by emphasizing different aspects of the same overall process.

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